Ginkgetin induces cell death in breast cancer cells via downregulation of the estrogen receptor

Abstract

Abstract. Ginkgetin is a natural biflavonoid isolated from the leaves of Ginkgo biloba, and is characterized by its anti-inflammatory and anti-viral activities. Although numerous studies state that it has also antitumor activity, the anti-proliferative effect of ginkgetin and the underlying mechanism in breast cancer cells have not yet been investigated. In the present study, ginkgetin inhibited the cell viability of MCF-7 and T-47D cells dose-dependently, and suppressed the expression of the estrogen receptor (ER) at the mRNA and protein levels. Among the targets of the ER, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), cyclin D1 and survivin were also downregulated by ginkgetin treatment. The anti-proliferative effects of ginkgetin were sufficient to suppress the growth by estradiol stimulation. However, ginkgetin did not significantly affect the viability of MDA-MB-231 cells, which are ER-negative cells. Furthermore, the knockdown of the ER and an inhibitor of PFKFB3 significantly sensitized MCF-7 and T-47D cells to ginkgetin. These findings suggest that ginkgetin induces cell death in ER-positive breast cancer cells via the inhibition of ER expression and that it is a promising agent for breast cancer treatment.

Icariin, an Up-and-Coming Bioactive Compound Against Neurological Diseases: Network Pharmacology-Based Study and Literature Review

“…41 Ginkgetin is a natural biflavonoid with anti-inflammatory, antiviral, and antitumor properties. 42 Icariin, a flavonoid glycoside, is the main bioactive ingredient of Epimedii herba and is a promising therapeutic agent for the treatment of various disorders because of its antiapoptotic, anti-inflammatory, and antioxidant activities. 43 , 44 …”

Identification and functional analysis of a biflavone as a novel inhibitor of transient receptor potential vanilloid 4-dependent atherogenic processes

“…Ginkgetin (GGT) was identified as one of the most potent inhibitors of TRPV4 in the screening. Since previously published reports showed that GGT has an anti-inflammatory and anti-adipogenic effect, we selected GGT for further functional analysis on TRPV4-dependent macrophage proatherogenic activity 48 , 49 , 52 , 53 .

Figure 1 Semi high-throughput screening-based identification of ginkgetin as a novel TRPV4 inhibitor from a library of natural compounds.

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Evaluation of Zamia floridana A. DC. Leaves and Its Isolated Secondary Metabolites as Natural Anti-Toxoplasma and Anti-Cancer Agents Using In Vitro and In Silico Studies

“…Four compounds of them were isolated for the first time from Z. floridana leaves. These compounds were tested previously in other studies against breast and colon cell lines in vitro and they showed cytotoxic effects [ 2 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 ], which could account for the cytotoxic effect of the n -butanol fraction of Z. floridana. The potent toxoplasmocidal effect of n -BuOH fraction encouraged us to investigate and predict the possible mechanisms of these compounds to inhibit T. gondii using in silico molecular docking study.…”